DESCRIPTION: During the Phase I proposal, hematopoietic re-agents were developed that supported the in vitro culture of sheep fetal tissue. With the culture system developed in Phase II, Dr. Brown and his Co-investigators are poised to answer significant questions in the Phase II proposal including: (l) The delineatian of the in vivo parameters for the proliferation and differentiation of hematopoietic stem cells (HSC) of fetal liver, spleen, and bone marrow: and (2) Assess the in vitro parameters that allow the expansion/homing that will facilitate the use of fetal and adult hematopoietic stem cells for in utero transplantations. The success of in utero transplantation of hematopoietic stem cells has been limited by the level and duration of cell engraftment that has been obtained. This Phase II proposal uses the sheep in utero model as has been shown to be highly unique in that it supports human multi- lineage differentiation. The re-agents and knowledge gained from the in vitro culture of fetal and adult hematopoietic stem cells to facilitate engraftment and expansion of specific hematopoietic stem cells will be of immense therapeutic value. Such reagents present do not exist. Development of these reagents are very timely and much needed to facilitate in utero transplantation research.